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Journal of Virology, July 2008, p. 6458-6469, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00068-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Multifunctional T-Cell Characteristics Induced by a Polyvalent DNA Prime/Protein Boost Human Immunodeficiency Virus Type 1 Vaccine Regimen Given to Healthy Adults Are Dependent on the Route and Dose of Administration{triangledown}

Anju Bansal,1 Bethany Jackson,1 Kim West,3 Shixia Wang,3 Shan Lu,3 Jeffrey S. Kennedy,3,4 and Paul A. Goepfert1,2*

Departments of Medicine,1 Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294,2 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655,3 Division of Molecular Medicine, New York State Department of Health, Albany, New York 122014

Received 10 January 2008/ Accepted 17 April 2008

A phase I clinical vaccine study of a human immunodeficiency virus type 1 (HIV-1) vaccine regimen comprising a DNA prime formulation (5-valent env and monovalent gag) followed by a 5-valent Env protein boost for seronegative adults was previously shown to induce HIV-1-specific T cells and anti-Env antibodies capable of neutralizing cross-clade viral isolates. In light of these initial findings, we sought to more fully characterize the HIV-1-specific T cells by using polychromatic flow cytometry. Three groups of participants were vaccinated three times with 1.2 mg of DNA administered intradermally (i.d.; group A), 1.2 mg of DNA administered intramuscularly (i.m.; group B), or 7.2 mg of DNA administered i.m. (high-dose group C) each time. Each group subsequently received one or two doses of 0.375 mg each of the gp120 protein boost vaccine (i.m.). Env-specific CD4 T-cell responses were seen in the majority of participants; however, the kinetics of responses differed depending on the route of DNA administration. The high i.m. dose induced the responses of the greatest magnitude after the DNA vaccinations, while the i.d. group exhibited the responses of the least magnitude. Nevertheless, after the second protein boost, the magnitude of CD4 T-cell responses in the i.d. group was indistinguishable from those in the other two groups. After the DNA vaccinations and the first protein boost, a greater number of polyfunctional Env-specific CD4 T cells (those with ≥2 functions) were seen in the high-dose group than in the other groups. Gag-specific CD4 T cells and Env-specific CD8 T cells were seen only in the high-dose group. These findings demonstrate that the route and dose of DNA vaccines significantly impact the quality of immune responses, yielding important information for future vaccine design.

* Corresponding author. Mailing address: Department of Medicine, University of Alabama at Birmingham, 908, 20th St. South, CCB 330, Birmingham, AL 35294. Phone: (205) 975-5667. Fax: (205) 975-5718. E-mail: paulg{at}uab.edu

{triangledown} Published ahead of print on 30 April 2008.

Journal of Virology, July 2008, p. 6458-6469, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00068-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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